How genes control development of nerve and muscle is an important and, as yet, unsolved question in biology and medicine. It has been inferred from many studies in both microbial and multicellular organisms that coding for proteins and the regulation of levels of specific proteins with respect to place and time represent molecular processes crucial to developmental mechanisms. The elucidation of how these mechanisms operate during the formation of the neuromuscular system in nematode worms during embryogenesis, larval growth, and adult maturation represents the principal objective of this program. In particular, biochemical, immunological, and physical studies of the contractile assembly in normal and mutant nematodes are envisaged. Appropriate mutations are to be selected on the basis of defective locomotion and resistance to stimulation at the neuromuscular junction. Isolation and characterization of contractile proteins from specific mutant animals in correlation with formal genetic mapping will establish which genetic loci actually code for actomyosin constituents. In contrast, other genetic elements are expressed as control mechanisms specific to the neuromuscular system. Three levels of control are of special interest in this program. Enzymes which covalently modify constituent polypeptide chains are expected to significantly direct the assembly of the c??c?~cci?e syscem, Rexu?~ci?? ?f cye ?~ces ?f si?sy?cyesis ~?u uex?~u~ci?? ?f cye c??c?~cci?e p??cei?s ~c key i?c?~ce??u?~? sices is ?esp??sis?e f?? cye ?sse?eeu sc?icyi?mec?y ?f my?fi?~me?cs ~?u cye ?~?xe i?c?e~ses i? musc?e m~ss uu?i?x x??fcy, Te?c~i? p~?~mece?s ?f cye sec??u~?y immu?e ?esp??se c? DN7 ~?e sei?x ex~mi?eu c?mp~?~ciee?y i? y?u?x ~uu?c ~?u ??u _24 m??cys) mice, Zc f~s f?u nd that the peak response of old mice was about 25% of that of young mice. The response of young mice was more sustained than that of old mice. No differences between the two age groups were found in the antigen dose required for optimal response or in the shape of the antigen dose response curve. Work planned includes an investigation of the numbers of precursors of antibody forming cells and of T cells, the susceptibility of B and T cells to tolerance induction, and other possible differences between young and old mice.